FIGURE 10-35 Mechanisms of RNA surveillance in the cytoplasm. (a) Nonsense-mediated decay. PTC = premature termination (stop) codon; SURF complex = complex of protein kinase SMG1, UPF1, and release factors eRF1 and eRF3. Formation of the SURF complex leads to phosphorylation of UPF1 by SMG1. The phosphorylated UPF1 associates with the UPF2-UPF3 complex bound to any exon-exon junction complexes that were not displaced from the mRNA by the first, pioneer ribosome to translate the message. This association leads to the association of the PTC-containing mRNA with P bodies, removal of the poly(A) tail, and degradation of the mRNA. (b) Non-stop decay. mRNAs that were prematurely cleaved and polyadenylated do not contain a stop codon before the poly(A) tail. When such mRNAs are translated, the ribosome translates the poly(A) tail and stalls at the 3′ end of the abnormal mRNA because the stop codon required for release factors eRF1 and eRF3 to associate with the ribosome A site is absent (see Figure 5-26). In higher eukaryotes, the factor Ski7 binds to the stalled ribosome and recruits the cytoplasmic exosome, which degrades the abnormal RNA step 1. Alternatively, in S. cerevisiae step 2, the displacement of PABPC1 from the poly(A) tail by the elongating ribosome leads to decapping and 5′→3′ degradation by the XRN1 exonuclease. (c) No-go decay. If a base of an mRNA is damaged so that a ribosome stalls there, or if an improperly processed mRNA has a stable stem-loop region with a long duplex stem that blocks elongation by the ribosome, the Dom34-Hbs1 complex binds the abnormal mRNA and makes an endonucleolytic cut in it. This cut generates a free 3′ end on the 5′ fragment, which is degraded by a cytoplasmic exosome, and a free 5′ end on the 3′ fragment, which is digested in the 5′→3′ direction by the XRN1 exonuclease. See N. L. Garneau, J. Wilusz, and C. J. Wilusz, 2007, Nat. Rev. Mol. Cell Biol. 8:113.